Pretransplant donor-specific helper T cell reactivity as a tool for tailoring the individual need for immunosuppression.

Background. A reliable immunological assay for quantification of donor-spec ific alloreactivity to identify patients at risk for future allograft rejec tion would be a helpful tool in organ transplantation. Therefore, we questi oned whether the T cell reactivity in patients measured before transplantat ion was predictive for the occurrence of acute rejection during the first y ear after kidney transplantation. Methods. The pretransplant T cell reactivity of peripheral blood mononuclea r cells to donor and third-party antigens was tested in mixed lymphocyte cu ltures, and to tetanus toxoid. In addition, we measured the frequency of do nor and third-party reactive helper T lymphocyte precursor and cytotoxic T lymphocyte precursors using limiting dilution analysis. Results. Patients who experienced acute rejection had significantly higher donor-specific mixed lymphocyte cultures responses (n=38; median stimulatio n index): 113 vs. 15, P=0.005) and helper T lymphocyte precursor frequency (n=37; median 194/10(6) vs. 62/10(6), P=0.009) measured before transplantat ion compared to patients without acute rejection. All patients with a low m ixed lymphocyte culture response (stimulation index less than or equal to 2 0; 13/13 vs. 12/25, P=0.001) and an undetectable helper T lymphocyte precur sor frequency (< 10/10(6) peripheral blood mononuclear cells; 7/7 vs. 17/30 , P=0.04) before transplantation did not experience acute rejection. The do nor-specific cytotoxic T lymphocyte precursor frequency (n=34; median 53/10 (6) vs. 28/10(6), P=0.58) and tetanus toxoid-reactivity (n=38; median stimu lation index: 53 vs.16, P=0.56) measured before transplantation did not cor relate with acute rejection. No correlation between third-party reactivity and acute rejection was observed. Conclusions. From. these results we conclude that despite the current HLA m atching criteria, undetectable helper T lymphocyte precursor frequency and low mixed lymphocyte culture responses against donor antigens measured befo re transplantation are predictive for a rejection-free first posttransplant year. These in vitro assays can be used to identify patients who require l ess immunosuppression after transplantation.